This study is to demonstrate the safety and tolerability of a single oral dose of BAY60-4552 in a single dose escalation design. Furthermore, this study examines the changes in hemodynamics after application of the test substance.42 hospitalized stable patients with chronic heart failure will be included. Several measurements will be performed to test how good the drug works and wether there are any unwanted reactions to the drug (e.g. blood tests, ECG, heart rate, blood pressure, adverse events). After a observation period the patient will be discharged from the hospital.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
55
Single dose escalation planned at dose of 1 mg, 2.5 mg, 5 mg, 7.5 mg, and 10 mg
Unnamed facility
Bad Nauheim, Hesse, Germany
Unnamed facility
Giessen, Hesse, Germany
Change in pulmonary capillary wedge pressure
Time frame: Pre-dose and up to 6 hr post-dose
Change in mean pulmonary artery pressure
Time frame: Pre-dose and up to 6 hr post-dose
AUC
Area under the plasma concentration vs time curve from zero to infinity after single dose
Time frame: Pre-dose and up to 72 hr post-dose
AUC/D
AUC divided by dose (mg)
Time frame: Pre-dose and up to 72 hr post-dose
Cmax
Maximum drug concentration in plasma after single dose administration
Time frame: Pre-dose and up to 72 hr post-dose
Cmax/D
Cmax divided by dose (mg)
Time frame: Pre-dose and up to 72 hr post-dose
Number of participants with adverse events
Time frame: Approximately 2 weeks
Mean right atrial pressure
Time frame: Pre-dose and up to 6 hr post-dose
Systolic pulmonary artery pressure
Time frame: Pre-dose and up to 6 hr post-dose
Diastolic pulmonary artery pressure
Time frame: Pre-dose and up to 6 hr post-dose
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Heart rate
Time frame: At pre-study visit, pre-dose and up to 24 hr post-dose
Cardiac output
Time frame: Pre-dose and up to 6 hr post-dose
Pulmonary vascular resistance
Time frame: Pre-dose and up to 6 hr post-dose
Pulmonary vascular resistance index
Time frame: Pre-dose and up to 6 hr post-dose
Systemic vascular resistance
Time frame: Pre-dose and up to 6 hr post-dose
Systemic vascular resistance index
Time frame: Pre-dose and up to 6 hr post-dose
Cardiac index
Time frame: Pre-dose and up to 6 hr post-dose
Mean arterial pressure
Time frame: Pre-dose and up to 6 hr post-dose
Systemic blood pressure
Time frame: At pre-study visit, pre-dose and up to 24 hr post-dose
Diastolic blood pressure
Time frame: At pre-study visit, pre-dose and up to 24 hr post-dose
Dyspnea Score
Subject is asked unpersuasively about his/her well-being in comparison to the baseline condition, measured on a 7-point Likert scale.
Time frame: Pre-dose and up to 48 hr post-dose
AUC(0-6)
AUC from time 0 to 6 h after study drug intake
Time frame: Pre-dose and up to 6 hr post-dose
AUCnorm
AUC divided by dose (mg) per kg body weight
Time frame: Pre-dose and up to 72 hr post-dose
AUC(0-tn)
AUC from time 0 to the last data point
Time frame: Pre-dose and up to 72 hr post-dose
AUC(0-tn)norm
AUC(0-tn) divided by dose (mg) per kg body weight
Time frame: Pre-dose and up to 72 hr post-dose
Cmax,norm
Cmax divided by dose (mg) per kg body weight
Time frame: Pre-dose and up to 72 hr post-dose
tmax
Time to reach maximum drug concentration in plasma after single dose
Time frame: Pre-dose and up to 72 hr post-dose
t½
Half-life associated with the terminal slope
Time frame: Pre-dose and up to 72 hr post-dose
Mean residence time
Time frame: Pre-dose and up to 72 hr post-dose
Total body clearance of drug from plasma calculated after oral administration (apparent oral clearance)
Time frame: Pre-dose and up to 72 hr post-dose
Apparent volume of distribution associated with the terminal phase (after oral administration)
Time frame: Pre-dose and up to 72 hr post-dose
Amount of drug excreted via urine
Time frame: Pre-dose and up to 6 hr post-dose
Percent amount of drug excreted via urine
Time frame: Pre-dose and up to 6 hr post-dose
Renal clearance of drug
Time frame: Pre-dose and up to 6 hr post-dose
Renin activity
Time frame: Pre-dose and up to 24 hr post-dose
Change from baseline of noradrenaline after drug administration
Time frame: Pre-dose and up to 24 hr post-dose
N-terminal pro-atrial natriuretic peptide
Time frame: Pre-dose and up to 24 hr post-dose
NT-pro B-type natriuretic peptide
Time frame: Pre-dose and up to 24 hr post-dose
Big endothelin-1
Time frame: Pre-dose and up to 24 hr post-dose
Cystatin C
Time frame: Pre-dose and up to 24 hr post-dose
Change from baseline of osteopontin after drug administration
Time frame: Pre-dose and up to 24 hr post-dose
Cyclic guanosine mono-phosphate
Time frame: Pre-dose and up to 24 hr post-dose